The use of
macrolides against
pneumonia has been reported to improve survival; however, little is known about their efficacy against methicillin-resistant Staphylococcus aureus (MRSA)
pneumonia. In this study, we investigated the effect of
azithromycin (AZM) and compared it with that of
vancomycin (VCM) and
daptomycin (DAP) in a murine model of MRSA
pneumonia. Mice were infected with MRSA by intratracheal injection and then treated with AZM, VCM, or DAP. The
therapeutic effect of AZM, in combination or not with the other drugs, was compared in vivo, whereas the effect of AZM on MRSA growth and toxin
mRNA expression was evaluated in vitro. In vivo, the AZM-treated group showed significantly longer survival and fewer bacteria in the lungs 24 h after
infection than the untreated group, as well as the other anti-MRSA
drug groups. No significant decrease in
cytokine levels (
interleukin-6 [IL-6] and
macrophage inflammatory protein-2 [MIP-2]) in bronchoalveolar lavage fluid or toxin expression levels (α-
hemolysin [Hla] and
staphylococcal protein A [Spa]) was observed following AZM treatment. In vitro, AZM suppressed the growth of MRSA in late log phase but not in stationary phase. No suppressive effect against toxin production was observed following AZM treatment in vitro In conclusion, contrary to the situation in vitro, AZM was effective against MRSA growth in vivo in our
pneumonia model, substantially improving survival. The suppressive effect on MRSA growth at the initial stage of
pneumonia could underlie the potential mechanism of AZM action against MRSA
pneumonia.